Around 11,000 participants also had MRI scans. In a Cambridge analysis of nearly 125,000 women, menopause was linked to more anxiety, depression and sleep disturbance, plus measurable differences in brain structure. The study, published in Psychological Medicine, drew on UK Biobank data and compared pre-menopausal women, post-menopausal women who had never used HRT, and post-menopausal women who had used it. The study still shows association, not cause and effect.
The average age of menopause onset in the sample was about 49.5 years. Women prescribed HRT started treatment at about 49.
Post-menopausal women reported more anxiety and depression than pre-menopausal women, were more likely to have seen a GP or psychiatrist for those symptoms, and were more likely to have formal diagnoses of anxiety or depression. Sleep followed the same pattern: post-menopausal women generally slept less and reported more insomnia. The HRT group reported even more mental-health symptoms than post-menopausal women not taking HRT, and they also reported the most tiredness.
Women who later started HRT already had more GP and psychiatrist visits for anxiety or depression before treatment began, which points to prescribing in response to existing distress. The British Menopause Society said HRT does not mitigate the observed effects, though it may slow the decline in reaction times, and it stressed that the study makes no claim about Alzheimer’s disease risk.
Post-menopausal women had smaller volumes in the hippocampus, entorhinal cortex and anterior cingulate cortex than pre-menopausal women, with the largest reductions in the HRT group. The imaging focus was the medial temporal lobe and anterior cingulate cortex. Memory scores changed only minimally across groups, and reaction times were only slightly slower in women not using HRT.
Menopause is common, affecting women mainly between 45 and 55, and Parliament has said around three quarters of women will have symptoms, with around a quarter experiencing severe symptoms. In England, about 15% of women aged 45 to 64 are prescribed HRT. NICE’s updated 2024 guidance now includes menopause-specific cognitive behavioural therapy for sleep problems and depressive symptoms.